This invention relates to crystalline, low melting, xcex5-caprolactone polymers bearing basic amine functionalities which are linked to the ester chain ionically or covalently to induce catalyzed hydrolysis. The ester components can be derived from xcex5-caprolactone with or without small amounts of glycolide, and/or or similar lactones. Such polymers with accelerated absorption profiles are especially adapted for use as transient coatings for absorbable multifilament surgical sutures (and other medical implants).
Multifilament surgical sutures such as Dexon(copyright) polyglycolide multifilament suture typically require a surface coating to improve their handling and knotting characteristics. Capitalizing on the desirable low melting temperature, crystallinity, and rheological properties of polycaprolactone and its copolymers as coating materials, several compositions based on this polymer were investigated as coatings for surgical sutures. Recognizing the fact that the xcex5-caprolactone homopolymer is essentially non-absorbable led to the development of copolymers of xcex5-caprolactone with variable amounts of more absorbable monomers to improve the coating absorbability. U.S. Pat. No. 4,624,256 discloses a suture coating copolymer of at least 90 percent xcex5-caprolactone and a biodegradable monomer and optionally a lubricating agent. Examples of monomers for the biodegradable polymers disclosed include glycolic acid and glycolide, as well as well-known monomers typically used to prepare absorbable polymer fibers or coatings for multifilament sutures. U.S. Pat. Nos. 4,788,979 and 4,791,929 disclose a bioabsorbable coating of a copolymer of at least 50 percent xcex5-caprolactone and glycolide. Sutures coated with such polymers are reported to be less stiff than sutures coated with other materials and the physical properties of the coated suture are also reported to be acceptable. U.S. Pat. No. 4,994,074 discloses copolymers of a predominant amount of xcex5-caprolactone, the balance being glycolide and glycolic acid. The use of glycolic acid as a comonomer into the copolymers of this invention was reported to increase the rate of absorption of the copolymer when used as a coating for multifilament surgical sutures.
Unfortunately, the problem of adequate bioabsorbability of xcex5-caprolactone-based polymers without detrimental effects on their desirable properties as coatings still remains. Specifically, the use of sufficient amounts of glycolide to achieve sufficient absorbability of the copolymeric coating can compromise its crystallinity and melting characteristics, for it may become amorphous or liquid near room temperature. On the other hand, the strategy of using glycolic acid to achieve the reported results in coating absorbability does limit the ability to produce sufficiently long chain molecules to achieve optimum frictional properties, due to glycolic acid""s known properties as both a ring-opening initiator chain terminator. Thus, a totally new approach to modifying the absorbability of polycaprolactone and its copolymers without affecting their desirable properties as suture coatings (or coatings for surgical devices) would be a more desirable goal.
The present invention provides a bioabsorbable, crystalline, nitrogenous copolyester lubricant coating for surgical devices, wherein the lactone derived component of the chain sequences are based on 90 percent to 98 percent xcex5-caprolactone-based units and 2 percent to 10 percent of glycolide-based units, having improved absorbability, as measured by rate or duration of sustained autocatalytic. In one embodiment of the present invention, improved absobabilility is provided the central location of the nitrogen of a tertiary amine, to which the polymer chains are covalently linked. The central, highly basic amine provides the maximum continued, sustained autocatalytic effect for the hydrolytic degradation of the copolyester chain. This embodiment of the invention is made using triethanolaine (TEA) as an initiator for the ring-opening polymerization of a mixture of cyclic monomers containing more than 85% xcex5-caprolactone.
In another embodiment of the present invention, improved absorbability is achieved by a copolyester polymer having two or more carboxylic groups per chain to which is ionically or covalently bound a basic amino acid. The increased number of basic amino acid groups per chain produces the improved absorbability. This structure highly absorbable structure is made using di- or tri- hydroxy acids as initiators. Use of these initiators doubles or triples the the carboxylic content of the polymeric chain over chains of comparable molecular weight made using glycolic acid.
The polymer molecular weight is less than 20 kDa. The coating may be advantageously applied to a variety of surgical devices, such as surgical sutures and staples, or facia fasteners as well as other surgical closure devices, and endovascular stents. In addition, the polyesters bearing the amine-functionalities which are the subject of this invention, and coatings derived therefrom, can be used alone or as carriers or matrices for viable cells and vaccines, or as a coating containing bioactive agents such as growth factors, antimicrobials and antibiotics.
Polyesters comprising predominantly xcex5-caprolactone polymer sequences generally refers to polymers with xcex5-caprolactone-based sequences of greater than 80 mole percent, the monomer compositions from which the polymers of this invention are derived. xcex5-Caprolactone is the predominant component of the polyester because of its low melting, exceptionally low glass transition temperature (Tg) and its ability to enhance the surface physical properties of coated multifilament sutures. Preferably, the amount of xcex5-caprolactone used in the synthesis of the polyester ranges from 90 to 99, more preferably, 96 to 99 mole percent. For copolyesters, of this invention, the remaining comonomers are preferably glycolide and/or glycolic acid. Other lactones such as lactide and p-dioxanone and/or their corresponding hydroxy acids can be used. The hydroxy acids can be used, specifically as chain initiators to control the polyester molecular weight, as determined in terms of their inherent viscosities (I.V.) as approximately 0.1 dl/g solutions in chloroform, and/or to provide chains with a carboxylic end group. The basic nitrogenous polyesters that are the subject of this invention, are to have I.V. or 0.05 to 0.35 dl/g and, preferably, 0.05 to 0.25 and, more preferably 0.10 to 0.20 dl/g.
The present invention deals with two definite improvements over the prior art disclosed in U.S. Pat. No. 6,197,320. The first improvement deals with use of di- or tri-carboxylic hydroxy acids as initiators for the ring-opening polymerization of a mixture of cyclic monomers containing more than 85% xcex5-caprolactone. Using di- or tri-carboxylic hydroxy acids as initiators, results in doubling or tripling the carboxylic content of the polymeric chain of comparable molecular weight made under similar conditions using glycolic acid. This, in turn, allows for including higher amounts of the basic amino acid per chain as counter ions of the carboxylate anions and hence, increases the rate of autocatalytic hydrolysis of the copolyester. The second improvement deals with the use of triethanolamine (TEA) as an initiator for the ring-opening polymerization of a mixture of cyclic monomers containing more than 85% xcex5-caprolactone. Using TEA as an initiator yields a nitrogenous copolyester with (1) symmetrically branched structure; and (2) a central 3xc2x0 amine group. This, in turn, increases the degree of toughness of the crystalline coating and minimizes its tendency to delaminate, particularly when used as a coating for braided sutures. Having a central, highly basic amine insures the availability of the amine group through most of the life of the copolyester and hence maximizes the continued sustained autocatalytic effect for hydrolytic degradation of the copolyester chain.
The coating can be applied to the braided suture as a low viscosity melt at temperatures between 70xc2x0 C. and 100xc2x0 C. and, preferably, 70xc2x0 C. and 90xc2x0 C. Excess coating can be removed by passing through a pad of non-woven fabric, e.g., polypropylene or a sizing die. More traditional methods of coating application can entail the use of 1 to 15 percent solution and, preferably, 2 to 10 percent in an organic solvent such as toluene at room temperature or between 25xc2x0 C. and 50xc2x0 C. Other solvents or mixture of solvents can be used as substitutes for toluene or acetone. The coated suture can be further treated thermally to insure even distribution of the coating on the braid components. Typical sutures which can be coated with the compositions which are the subject of this invention include those made of polyglycolide and polyethylene terephthalate. Depending on the suture size, the percent add-on of the coating can be varied between 1 and 10 percent and, preferably, 1.5 to 4.5 percent as the suture decreases from about size #1 to about size #6-0. At such level of coating, the suture handling and tie-down characteristics are improved substantially without compromising other properties such as pliability, surface appearance, and knot strength and security.
The coatings which are the subject of this invention can be used to coat synthetic multifilament yarn constructed for use as a dental floss using a similar application protocol to those used for suture coating. For dental floss, a higher coating add-on than those used for suture is preferred in certain constructions and sizes.
The absorption profile of the coating is such that it will not affect that of an absorbable suture to any discernable extent. Typically, when representative coatings subject of this invention are used on polyethylene terephthalate sutures incubated in a phosphate buffer at 37xc2x0 C. and pH of 7.25 lose 50 to 100 percent of their original mass in two to six months.
The following examples illustrate the claimed invention and are in no way intended to limit its scope.